Assessment of Risk Factors and Clinical Importance of Enlarged Perivascular Spaces by Whole-Brain Investigation in the Multi-Ethnic Study of Atherosclerosis
Authors: Sokratis Charisis, Tanweer Rashid, Hangfan Liu, Jeffrey B. Ware, Paul N. Jensen, Thomas R. Austin, Karl Li, Elyas Fadaee, Saima Hilal, Christopher Chen, Timothy M. Hughes, Jose Rafael Romero, Jon B. Toledo, Will T. Longstreth, Timothy J. Hohman, Ilya Nasrallah, R. Nick Bryan, Lenore J. Launer, Christos Davatzikos, Sudha Seshadri, Susan R. Heckbert, Mohamad Habes
Journal: JAMA Network Open (2023)

Importance Enlarged perivascular spaces (ePVSs) have been associated with cerebral small-vessel disease (cSVD). Although their etiology may differ based on brain location, study of ePVSs has been limited to specific brain regions; therefore, their risk factors and significance remain uncertain. Objective Toperform a whole-brain investigation of ePVSs in a large community-based cohort. Design, Setting, and Participants This cross-sectional study analyzed data from the Atrial Fibrillation substudy of the population-based Multi-Ethnic Study of Atherosclerosis. Demographic, vascular risk, and cardiovascular disease data were collected from September 2016 to May 2018. Brain magnetic resonance imaging was performed from March 2018 to July 2019. The reported analysis was conducted between August and October 2022. A total of 1026 participants with available brain magnetic resonance imaging data and complete information on demographic characteristics and vascular risk factors were included. Main Outcomes and Measures Enlarged perivascular spaces were quantified using a fully automated deep learning algorithm. Quantified ePVS volumes were grouped into 6 anatomic locations: basal ganglia, thalamus, brainstem, frontoparietal, insular, and temporal regions, and were normalized for the respective regional volumes. The association of normalized regional ePVS volumes with demographic characteristics, vascular risk factors, neuroimaging indices, and prevalent cardiovascular disease was explored using generalized linear models. Results In the 1026 participants, mean (SD) age was 72 (8) years; 541 (53%) of the participants were women. Basal ganglia ePVS volume was positively associated with age (β = 3.59 × 10 −3 ; 95% CI, 2.80 × 10 −3 to 4.39 × 10 −3 ), systolic blood pressure (β = 8.35 × 10 −4 ; 95% CI, 5.19 × 10 −4 to 1.15 × 10 −3 ), use of antihypertensives (β = 3.29 × 10 −2 ; 95% CI, 1.92 × 10 −2 to 4.67 × 10 −2 ), and negatively associated with Black race (β = −3.34 × 10 −2 ; 95% CI, −5.08 × 10 −2 to −1.59 × 10 −2 ). Thalamic ePVS volume was positively associated with age (β = 5.57 × 10 −4 ; 95% CI, 2.19 × 10 −4 to 8.95 × 10 −4 ) and use of antihypertensives (β = 1.19 × 10 −2 ; 95% CI, 6.02 × 10 −3 to 1.77 × 10 −2 ). Insular region ePVS volume was positively associated with age (β = 1.18 × 10 −3 ; 95% CI, 7.98 × 10 −4 to 1.55 × 10 −3 ). Brainstem ePVS volume was smaller in Black than in White participants (β = −5.34 × 10 −3 ; 95% CI, −8.26 × 10 −3 to −2.41 × 10 −3 ). Frontoparietal ePVS volume was positively associated with systolic blood pressure (β = 1.14 × 10 −4 ; 95% CI, 3.38 × 10 −5 to 1.95 × 10 −4 ) and negatively associated with age (β = −3.38 × 10 −4 ; 95% CI, −5.40 × 10 −4 to −1.36 × 10 −4 ). Temporal region ePVS volume was negatively associated with age (β = −1.61 × 10 −2 ; 95% CI, −2.14 × 10 −2 to −1.09 × 10 −2 ), as well as Chinese American (β = −2.35 × 10 −1 ; 95% CI, −3.83 × 10 −1 to −8.74 × 10 −2 ) and Hispanic ethnicities (β = −1.73 × 10 −1 ; 95% CI, −2.96 × 10 −1 to −4.99 × 10 −2 ). Conclusions and Relevance In this cross-sectional study of ePVSs in the whole brain, increased ePVS burden in the basal ganglia and thalamus was a surrogate marker for underlying cSVD, highlighting the clinical importance of ePVSs in these locations.